The FDA has granted Priority Review to the combination of Enhertu (trastuzumab deruxtecan) plus pertuzumab for first-line treatment of HER2-positive metastatic breast cancer, with a PDUFA target action date of April 28, 2025. This represents a potential paradigm shift toward ADC-based regimens in the frontline setting, moving away from traditional chemotherapy backbones.
Drug Profile & Mechanism
- Enhertu: HER2-directed antibody-drug conjugate (ADC) combining trastuzumab with a topoisomerase I inhibitor payload
- Pertuzumab: HER2-directed antibody that blocks HER2 dimerization
- Target Population: Adults with HER2-positive unresectable or metastatic breast cancer
- Mechanism Synergy: Dual HER2 blockade without traditional chemotherapy, potentially reducing toxicity while maintaining efficacy
- Partnership: Co-developed by AstraZeneca and Daiichi Sankyo
Regulatory Milestone Details
- Designation: FDA Priority Review granted (6-month expedited timeline vs. standard 10 months)
- Supporting Data: Based on Phase III DESTINY-Breast09 trial results
- PDUFA Date: April 28, 2025
- Current Status: Enhertu already approved in U.S. for second-line HER2+ metastatic breast cancer and other HER2+ tumor types
- Trial Results: DESTINY-Breast09 demonstrated statistically significant and clinically meaningful improvement in progression-free survival (PFS) vs. standard of care
Practice Implications
- Treatment Sequencing Impact: May establish ADC + pertuzumab as new first-line standard, relegating taxane-based regimens
- Toxicity Profile: Potential for improved tolerability by eliminating traditional chemotherapy
- Patient Selection: Could broaden first-line options for patients unable to tolerate intensive chemotherapy
- Guideline Impact: Likely to influence NCCN and ASCO guideline recommendations for first-line HER2+ metastatic breast cancer
- Access Considerations: Approval would make this combination available approximately 6 months earlier than standard review timeline
Development Status & Next Steps
- Regulatory Timeline: Decision expected by April 28, 2025
- Global Development: Regulatory submissions in other regions anticipated
- Ongoing Trials: DESTINY-Breast09 data may support additional indications
- Market Impact: First-line approval would significantly expand Enhertu’s treatment landscape
- Evidence Maturation: Overall survival data and longer-term safety profiles will inform optimal positioning
